Five Year Outcomes in Patients with End Stage Renal Disease Who Received a Bioengineered Human Acellular Vessel for Dialysis Access

Abstract

Objective: Patients with end stage renal failure who require haemodialysis suffer morbidity and mortality due to vascular access. Bioengineered human acellular vessels (HAVs) may provide a haemodialysis access option with fewer complications than other grafts. In a prospective phase II trial from 2012 to 2014 (NCT01744418), HAVs were implanted into 40 haemodialysis patients at three sites in Poland. The trial protocol for this "first in man" use of the HAV contemplated only two years of follow up, and the trial results were initially reported in 2016. In light of the retained HAV function seen in many of the patients at the two year time point, follow up for patients who were still alive was extended to a total of 10 years. This interim follow up report, at the long term time point of five years, assessed patient and conduit status in those who continued routine dialysis with the HAV.

Methods: HAVs are bioengineered by culturing human vascular smooth muscle cells on a biodegradable polymer matrix. In this study, patients with patent HAV implants at 24 months were followed every three months, starting at month 27 through to month 60, or at least five years post-implantation. This report contains the follow up functional and histological data on 29 of the original 40 patients who demonstrated HAV function at the 24 month time point.

Results: Eleven patients completed at month 60. One patient maintained primary patency, and 10 maintained secondary patency. Secondary patency was estimated at 58.2% (95% confidence interval 39.2-73.1) at five years, after censoring for deaths (n = 8) and withdrawals (n = 1). No HAV conduit infections were reported during the follow up period.

Conclusion: This phase II long term follow up shows that the human acellular vessel (HAV) may provide durable and functional haemodialysis access for patients with end stage renal disease.

Keywords: Blood vessel prosthesis; Haemodialysis; Regenerative medicine; Tissue engineering; Vascular access.

Figure 1

Patient disposition (CONSORT diagram). HAV = human acellular vessel; I/E = inclusion/exclusion.

Figure 2

Six years of haemodialysis using a human acellular vessel. (A1) Skin over the human acellular vessel (HAV), which has been used for haemodialysis for approximately six years (subject 02-010); black arrow indicates a cannulation zone subjected to needle punctures over the years. (A2) Ultrasound images of the vessel from the same patient, with the conduit diameter being 8–9 mm, greater than the original implantation inner diameter of 6 mm (note cursors extend outside the vessel lumen). (B1, B2) HAV cross sections at 122 weeks. (C1) Immunofluorescence staining in samples explanted at 200 weeks for endothelial progenitor marker CD34 (green) and the endothelial maker CD31 (red) demonstrate CD31⁺ endothelial cells with neovascularisation present in both the adventitial and medial layer of the HAV. (C2) Immunofluorescence staining for alpha smooth muscle actin (αSMA; red) and calponin 1 (CNN1; green), markers associated with vascular smooth muscle cells, in samples explanted at 200 weeks. In (C1) and (C2) images, nuclei (blue) were counterstained with 4′,6-diamidino-2-phenylindole (DAPI).